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B cell signature contributes to the prediction of RA development in patients with arthralgia
  1. Joyce Lübbers1,
  2. Saskia Vosslamber1,
  3. Lotte A van de Stadt2,
  4. Marian van Beers-Tas2,
  5. John G Wesseling1,
  6. B Mary E von Blomberg1,
  7. Birgit I Witte3,
  8. Hetty J Bontkes1,
  9. Dirkjan van Schaardenburg2,4,
  10. Cornelis L Verweij1,5
  1. 1 Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
  2. 2 Jan van Breemen Research Institute | Reade, Amsterdam, The Netherlands
  3. 3 Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
  4. 4 Department of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam, The Netherlands
  5. 5 Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands
  1. Correspondence to Dr Cornelis L Verweij, Department of Pathology and Rheumatology, VU University Medical Center, Section of Inflammatory Disease Profiling, CCA2.28, P.O. box 7075, Amsterdam 1007 MB, The Netherlands; c.verweij{at}

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Early recognition followed by treatment of rheumatoid arthritis (RA) helps to maintain joint integrity and functional capacity,1 suggesting it may be beneficial to intervene in patients with arthralgia before RA develops. Anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) are established predictive markers,2 ,3 but only 20–40% of ACPA and/or RF positive patients with arthralgia develop RA within 2 years.4 Recently, we have demonstrated that the type I interferon (IFN) signature correctly identifies 52% of patients with arthralgia who will develop RA within 2 years.5 ,6 Our previous study suggested that a B cell related gene signature was associated with protection against arthritis development,6 and could aid in the prediction of arthritis development. We therefore studied the clinical value of the B cell signature, comprising CD19, CD20, CD79α and CD79β, for the prediction of arthritis development in an independent cohort of 115 ACPA and/or RF positive patients with arthralgia followed for median 22 months5 and explored the phenotypical nature of this B cell signature. In total, 44 patients (38%) developed arthritis (defined as one or more swollen joints) within 2 years. Of these, 4 patients had undifferentiated arthritis and 40 patients fulfilled the 2010 American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) criteria for RA. Patients were stratified into B cellhigh …

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  • Funding This research was performed with support from the ‘TRACER’ consortium in the framework of the Center for Translational Molecular Medicine (CTMM) (

  • Competing interests DvS and CLV are inventors on a patent application, where the use of the gene signatures for the diagnosis of preclinical RA is described.

  • Patient consent Obtained.

  • Ethics approval Centrale Commissie Mensgebonden Onderzoek Slotervaartziekenhuis en Reade.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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